Lenalidomide-Refractory Multiple Myeloma

Keith Stewart, MBChB: I’m surprised nobody mentioned daratumumab with bortezomib earlier. That hasn’t even been brought up as an option in a lenalidomide-refractory patient. Noopur, I’ll pick on you again. Why not use that?

Nooper Raje, MD: Well, part of the reason for not using that is that most of our patients have been exposed to bortezomib already up front. The issues around toxicity of bortezomib for long-term use is something we’ve talked about, the neuropathy specifically. If you look at the old data with bortezomib-daratumumab, although it was a positive trial, the data were not that impressive. In the CANDOR and the IKEMA studies, the data look much better. We tend to use carfilzomib at the time of relapse now. That might change with more people using KRd [carfilzomib, lenalidomide, dexamethasone] up front. But for right now, the go-to proteasome inhibitor seems to be carfilzomib at the time of first relapse.

Keith Stewart, MBChB: Many of you mentioned using pomalidomide. Tom, why not just use lenalidomide again? I gave the case where somebody was progressing on it, so I made it easy. But if you had lenalidomide and stopped it, would you use pomalidomide at relapse, or would you go back and use lenalidomide again?

Thomas G. Martin, MD: If there’s been a significant 6- to 12-month break, and they’re truly not refractory to lenalidomide, it’s acceptable to give that a try, as long as they didn’t have toxicity to the lenalidomide. Pomalidomide is tolerated a little better than lenalidomide. I prefer it when they do have relapse. I tend to do that even if they’ve been off lenalidomide for a while.

Keith Stewart, MBChB: It’s been my experience that there may be more neutropenia, where I don’t know if it’s compared with lenalidomide. But when you use pomalidomide with daratumumab, for example, that can be a bit of a challenge. Anybody else want to comment?

Natalie S. Callander, MD: Yes, I agree with what Tom says. A lot of people who are on long-term lenalidomide hate the GI [gastrointestinal] adverse effects: chronic surprise diarrhea and things like that. Pomalidomide really doesn’t seem to have that. A lot of patients appreciate that. If I have a patient who’s had a long-term response on lenalidomide maintenance after a transplant and then stopped maintenance, and they start to have a biochemical relapse, those are people I will give lenalidomide again to.

Nooper Raje, MD: Most of us want to use the most active drug. Pomalyst is certainly more active than lenalidomide. Now we have the new CELMoDs [CRBN modulating agents]. The worry used to be, what are you going to do next? We have really active CELMoDs coming down the pike. So I would go to pomalidomide.

Keith Stewart, MBChB: A CELMoD is a third-generation version of thalidomide-lenalidomide-pomalidomide, with maybe some slightly different biological effects. But there are some very potent ones out there in clinical trials. Iberdomide is the 1 we’ve heard the most about, showing some activity even in people who’ve failed pomalidomide. Pomalidomide sounds like a good choice. What else have you combined it with, Natalie?

Natalie S. Callander, MD: Based on the OPTIMISMM trial, we use some Velcade. I know you mentioned that people aren’t using Velcade. We will give pomalidomide with Velcade, typically in a person who hasn’t had previous neuropathy. One of the regimens that we’ve used in older people, and I don’t know if other people have done this, is an old [Antonio] Palumbo regimen: pomalidomide with oral cyclophosphamide and prednisone, which is a triplet regimen you can give older patients. It’s very well tolerated.

Peter Voorhees, MD: The data with elotuzumab-pomalidomide-dexamethasone are quite good. There’s a clear difference in overall response and a very significant difference in median progression-free survival with the addition of the elotuzumab. As Tom alluded to before, the toxicity profile of elotuzumab is quite favorable. The challenge with elotuzumab-pomalidomide-dexamethasone is that it’s unclear what its activity is and what its role is going to be in a post-CD38 antibody world, which is where most of us are using it. Anecdotally, my experience with elotuzumab-pomalidomide-dexamethasone in daratumumab-refractory patients has been suboptimal.

Keith Stewart, MBChB: We’ve concluded that pomalidomide can be combined with a number of different drugs. It seems to be the IMiD [immunomodulatory imide drug] of choice at relapse among the group, and it’s pretty active and certainly a good choice in this situation.

Transcript edited for clarity.